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Martin\u2013Hopkins and Sampson-NIH equations were shown to outperform Friedewald\u2019s in various populations. Our aim was to derive a novel equation for accurate LDL-C estimation in Saudi Arabians and to compare it to Friedewald, Martin\u2013Hopkins and Sampson-NIH equations. This is a cross-sectional study on 2245 subjects  who\u00a0were allocated to 2 cohorts; a derivation (1) and a validation cohort (2). Cohort 1 was analyzed in a multiple regression model to derive an equation (equation<jats:sup>D<\/jats:sup>) for estimating LDL-C. The agreement between the measured (LDL-C<jats:sup>DM<\/jats:sup>) and calculated levels was tested by Bland\u2013Altman analysis, and the biases by absolute error values. Validation of the derived equation was carried out across LDL-C and triglyceride (TG)-stratified groups. The mean LDL-C<jats:sup>DM<\/jats:sup> was 3.10\u2009\u00b1\u20091.07 and 3.09\u2009\u00b1\u20091.06 mmol\/L in cohorts 1 and 2, respectively. The derived equation is: LDL-C<jats:sup>D<\/jats:sup>\u2009=\u20090.224\u2009+\u2009(TC \u00d7 0.919) \u2013 (HDL-C \u00d7 0.904) \u2013 (TG \u00d7 0.236) \u2013 (age \u00d7 0.001) \u2013 0.024. In cohort 2, the mean LDL-C (mmol\/L) was estimated as 3.09\u2009\u00b1\u20091.06 by equation<jats:sup>D<\/jats:sup>, 2.85\u2009\u00b1\u20091.12 by Friedewald, 2.95\u2009\u00b1\u20091.09 by Martin\u2013Hopkins, and 2.93\u2009\u00b1\u20091.11 by Sampson-NIH equations; statistically significant differences between direct and calculated LDL-C was observed with the later three equations (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Bland\u2013Altman analysis showed the lowest bias (0.001 mmol\/L) with equation<jats:sup>D<\/jats:sup> as compared to 0.24, 0.15, and 0.17 mmol\/L with Friedewald, Martin\u2013Hopkins, and Sampson-NIH equations, respectively. The absolute errors in all guideline-stratified LDL-C categories was the lowest with equation<jats:sup>D<\/jats:sup>, which also showed the best classifier of LDL-C according to guidelines. Moreover, equation<jats:sup>D<\/jats:sup> predicted LDL-C levels with the lowest error with TG levels\u00a0up to 5.63 mmol\/L. Equation<jats:sup>D<\/jats:sup> topped the other equations in estimating LDL-C in Saudi Arabians as it could permit better estimation when LDL-C is\u2009&lt;\u20092.4 mmol\/L, in familial hyperlipidemia, and in hypertriglyceridemia, which improves cardiovascular outcomes in high-risk patients. We recommend further research to validate equation<jats:sup>D<\/jats:sup> in a larger dataset and in other populations.<\/jats:p>","DOI":"10.1038\/s41598-024-55921-w","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T20:01:45Z","timestamp":1709668905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel equation for the estimation of low-density lipoprotein cholesterol in the Saudi Arabian population: a derivation and validation study"],"prefix":"10.1038","volume":"14","author":[{"given":"Dena A.","family":"Nuwaylati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuhier A.","family":"Awan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"55921_CR1","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","volume":"80","author":"M Vaduganathan","year":"2022","unstructured":"Vaduganathan, M., Mensah, G. 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